Biologic scaffolds composed of extracellular matrix (ECM) which represents the secreted products of resident cells of each tissue and organ, are increasingly used in regenerative medicine strategies for tissue and organ replacement. Preservation of the native ultrastructure and composition of ECM during the process of tissue decellularization is highly desirable (Ott et al., Nat. Med., 14:213 (2008); Uygun et al., Nat. Med., 16:814 (2010); Petersen et al., Science, 329:538 (2010); Nakayama et al., Tissue Eng. Part A, 16:2207 (2010); Allen et al., Tissue Eng. Part A, 16:3363 (2010); Simionescu et al., J. Heart Valve Dis., 12:226 (2003); Badylak et al., Acta Biomater., 5:1 (2009)). Numerous methods have been employed to decellularize tissues and organs and those methods may result in decellularized tissues and organs with different mechanical and biological properties. For example, certain chemicals and solutions, e.g., acids, bases, hypotonic solution, hypertonic solution, detergents, alcohols, chelating agents, and other solvents, enzymes such as nucleases, collegenases and lipases, and physical treatments including temperature, force and pressure, non-thermal electroporation, have been employed to decellularize tissues and organs.
Autograft bone long has been the preferred implant for most bone graft procedures in the United States. Autograft bone is a desirable graft source because it provides a scaffold for osteoconduction, contains noncollagenous bone matrix proteins that stimulate osteoinduction, and incorporates progenitor stem cells for osteogenesis.
Despite its wide prevalence, the use of autograft material poses several disadvantages. At best, the need to harvest the autograft from the iliac crest, proximal tibia or distal femur presents the obvious drawbacks of the discomfort, time and expense of two procedures to accommodate the patient's need for bone grafting. At worst, the initial harvesting procedure can precipitate chronic pain, significant blood loss, infection and other iatrogenic complications, prolonged hospital stay and recovery time. The second surgery also adds substantially to the cost of the overall bone graft process. Additionally, the autograft material is collected in fragments, which is sufficient as a bone filler for small voids, but offers minimal structural stability.
While cadaver-derived allograft, the second most frequent material, precludes the need for a second surgery and can be used for large, load bearing applications, the grafted bone may be incompatible with, and ultimately rejected by, the host bone due to the cellular material still present. In addition, the effectiveness of allograft material is inconsistent. The processing of allograft tissue to lower contamination risk also can substantially degrade the biologic and mechanical properties initially present in the donated tissue.
The inherent shortcomings of both autografts and allografts have driven the development of synthetic bone graft substitutes, however, synthetic materials are currently used in only ten percent of orthopedic procedures worldwide. Biosynthetic and synthetic materials now available to orthopedic and spinal surgeons include demineralized bone matrix, collagen, ceramics, cements, and polymers, such as silicone and some acrylics. These materials can serve as a structure on which new bone can grow. Many of these materials then dissolve over time, leaving new bone behind. The benefits of these synthetic grafts include availability, sterility and reduced morbidity. However, many of them lack the osteoinductive properties of native bone.